Gene activity offers a window into kidney transplants

Prof Barbara Murphy, chair of the Samuel Bronfman Department of Medicine, the Murray M Rosenberg Professor of Medicine and the Dean of Clinical Integration and Population Management at the Icahn School of Medicine at the Mount Sinai Health System in New York

Your research is looking to improve kidney transplants, what are you doing?

“We are developing new ways to predict when a transplanted kidney is likely to become damaged over the long term, so the person who received the kidney can be managed more effectively in order to prolong the survival of that organ. The hope then is they will not need another transplant as quickly or hopefully not at all.

How are you going about that?

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We have been looking both at biopsies from kidneys following transplant and also at blood samples from recipients. We are finding patterns of genes that are being switched on that can tell us if a person is at higher risk of rejecting that kidney either acutely in the short term, or if they are at risk of the kidney becoming chronically damaged over the longer term.

How has the work been going?

Really well. We have published some big studies – one in The Lancet – and we are in the process of submitting another two studies. In the Lancet study, we found that a gene profile in biopsies taken from the recipients three months after the transplant was able to predict their risk of the kidney being damaged by a year after the transplant. The idea is that you can then use this profile to treat the recipients who are at risk, with the aim of protecting the kidney and thereby preventing it from failing.

And what about the blood samples?

We have been looking at gene activity in blood because it’s an easier sample for patients to give than a kidney biopsy. That work has been going well, we have found a set of genes that are active in the blood that can tell even before a person has had a transplant how likely they are to have a rejection episode after transplantation.

What is the big reward of doing all this work?

Well, we would hope that thanks to the approach we are taking it will be possible to stratify patients into high and low risk before a transplant, and then treat them appropriately at the time of the transplant and monitor them more closely overall. That would hopefully lead to less rejection and damage of kidneys. It would also mean that people that were low risk could avoid unnecessary exposure to high levels of immunosuppression and as a result decrease their risk of infection and cancer.

And the challenges?

The time it takes. I applied for the funding to start this research back in 2005 and we started in 2008. It took a long time to set everything up and enrol patients and follow them over time, to take the biopsies and the blood and analyse the results. You also always need to be thinking of what it takes to translate these assays into clinical care. It often means seeking investment from companies and setting up trials across multiple centres so you can demonstrate the true impact.

You received an honorary doctorate from the Royal College of Surgeons in Ireland last month, how did that feel?

It was brilliant, to get this award from my alma mater was wonderful. My husband and our son were there for it, and my mum and dad too, which made it even more special.

And how do you like to get a break from all the research?

I like mainly outdoorsy things: biking, hiking, gardening. We are based in New York but we have a place in Vermont and that is where you can totally switch off. We love going up there.